Page 60 - Color Atlas Of Pathophysiology (S Silbernagl Et Al, Thieme 2000)

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the guise of adhesion molecules, cause the leu- locally and chemotactically, but also include
kocytes to roll along the endothelium and thus the entire organism in the inflammation reac-
activate other adhesion molecules (integrins; tion (acute-phase response; → A). Mediated by
ICAM-1, VCAM). This enables the leukocytes IL-1, IL-6, and TNF-α, the following occurs via
to adhere to the vessel wall (margination). The specific receptors:
increased endothelial permeability (loosening – Sleep reactions are initiated in the brain
of endothelial cell connections) allows the leu- (fatigue, tiredness);
kocytes to slip through into the extravascular – The set point of the body temperature shift-
space (diapedesis; → A). Furthermore, more ed towards higher levels (fever; → p. 20);
protein-rich fluid (inflammatory exudate) – Bone marrow is stimulated to release
reaches the interstitial spaces and leads to more leukocytes;
edematous swelling. In extreme cases even – The liver is stimulated to absorb more iron
the erythrocytes leave the blood vessels (hem- (taking it from the bacteria in plasma) and
orrhagic inflammation). Finally, pain arises, to produce so-called acute-phase proteins
which brings the injury into consciousness (among them C reactive protein [CRP] and
(changed behavior), and stimulates a reflex ac- serum amyloid A [SAA]);
tion to nurse the inflammed region (e.g., a – The immune system is stimulated
limb). (e.g., antibodies are formed); and
The neutrophils that have migrated to the – Lipolysis and catabolism are initiated
site of inflammation and the macrophages (weight loss).
Blood that have differentiated from the immigrant Tissue repair. After transient formation of cell-
monocytes now try to phagocytize the patho-
3 gens causing the inflammation and to digest rich granulation tissue (macrophages etc.),
them by means of their lysosomes. Their “ap- characterized by budding blood vessels, plate-
petite” is increased by opsonification with IgG let-derived growth factor (PDGF) and other
or C3b (→ p. 44). mediators stimulate the proliferation and im-
The complement system is also activated by migration of fibroblasts. They produce glycos-
the inflammation, in the classical way in the amineglycans that swell and deposit them-
presence of antigen–antibody complexes or in selves on collagen fibers. New collagen is also
the slower, so-called alternative way through formed; shrinking of this collagen closes the
less specific binding to bacteria-infected or wound margins.
virus-infected cells. In both cases complement Finally, the collagen fibers (scar) are re-
C3b is formed. It not only opsonizes antigens, placed by normal tissue for that site (restitutio
but also causes polymerization of other com- ad integrum; → B). This latter event is, how-
ponents (C5–C9) on the cell membrane of the ever, true only for small, noninfected tissue in-
attacking pathogen which forms the mem- juries. If the cause of the inflammation (e.g.,
brane-attack complex and thus triggers lysis foreign bodies or wound infection) cannot be
of the pathogen (→ p. 44). The complement removed at once, wound healing is delayed
system can, in addition, break up virus parti- and the defense response by the phagocytes is
cles and antigen–antibody complexes. Side intensified. Much energy is expended in this
products of the complement system (C3a, (increased warming), the synchronously
C4a and C5a, so-called anaphylaxins) act che- activated hemostatic system occludes vessels
motactically and activate macrophages. in the surrounding area so that ATP also be-
Macrophages are activated mainly by path- comes deficient due to a lack of O 2 , and the
ogen exotoxins and endotoxins and by anti- pH value falls (anerobic lactic acid formation).
gen–antibody complexes, C5a, crystals (see The liberated oxidants also damage the body’s
above), and by phagocytosis, whereupon oxi- own cells. When these die, lysosomal enzymes
–
1
dants like O 2 , OH·, O 2 , and H 2 O 2 are liberated are freed so that finally the leukocytes and
and damage the pathogens (→ A). The macro- cells of the inflamed tissue themselves also
phages also release inflammation mediators, die. This tissue death (necrosis), which can pro-
50 for example, PAF, leukotrienes, prostaglandins, gress to abscess formation (→ B), is the price
IL-1, IL-6, and TNF-α. The latter do not only act paid for preventing the spread of inflamma-
Silbernagl/Lang, Color Atlas of Pathophysiology © 2000 Thieme
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